A hallmark of many diseases is genomic instability leading to changes in the structure and content of the DNA or mutations. Mutations lead to the chain of events associated with cancer: tumor formation, vascularization, outgrowth, and metastasis. Additionally, during bacterial infections resistance to antibiotics arises due to stres- induced genomic instability. In the long term, understanding the basis of how DNA mutations occur will provide new diagnostic tools for the clinician, targets for chemotherapies, and increase our understanding of disease. DNA mutations in cancer cells, antibiotic resistance, and pathogen evolution are analogous to mutations occurring in the bacterium, Escherichia coli during nutritional stress. We propose a plan of research that will identify the cellular components responsible for DNA mutations in E. coli during nutritional stress. These proteins may represent new classes of targets for the chemotherapeutic treatment of cancers and bacterial infections.